Asian Sand Dust Upregulates IL-6 and IL-8 via ROS, JNK, ERK, and CREB Signaling in Human Nasal Fibroblasts.

Abstract

Background Asian sand dust (ASD) profoundly affects respiratory health by inducing inflammation and causing upper airway inflammatory diseases. Interleukin (IL)-6 and IL-8 are pro-inflammatory mediators that are involved in upper airway inflammatory diseases. However, the effect of ASD on the production of IL-6 and IL-8 in nasal fibroblasts has not been adequately studied. We investigated the effect of ASD on the induction of pro-inflammatory mediators and its underlying mechanisms in nasal fibroblasts. Methods Real-time cytotoxicity assays were used to determine the effect of ASD on the viability of fibroblasts. Enzyme-linked immunosorbent assays and real-time polymerase chain reactions were performed to determine whether ASD induced the expression of IL-6 and IL-8. Reactive oxygen species (ROS) were quantified using 2, 7-dichlorofluorescein-diacetate and MitoSOX Red. Induction of IL-6 and IL-8 signal transduction pathways by ASD was confirmed by Western blotting. Ex vivo culture of the inferior turbinate tissue was performed to confirm the effects of ASD. Results ASD upregulated ROS levels, and this in turn promoted IL-6 and IL-8 expression through the MAPK (JNK and ERK) and CREB signaling pathways in nasal fibroblasts. However, ASD did not induce phosphorylation of p38. Specific inhibitors of each pathway (ROS, JNK, ERK, and CREB inhibitors) suppressed ASD-induced IL-6 and IL-8 upregulation. Conclusions ASD induces pro-inflammatory mediators, and the increased levels of IL-6 and IL-8 might be associated with the pathogenesis of chronic rhinosinusitis.